Hypodermic ampoule with skin tensioning clip

ABSTRACT

Hypodermic ampoules of the contained-needle type, and combinations of such ampoules with so-called &#39;&#39;&#39;&#39;applicators&#39;&#39;&#39;&#39; for actuating the ampoules to make injections are disclosed. Each of several ampoule forms has at least one cylindrical, medicamentcontaining chamber and a plunger closing one end thereof. A hollow needle is fixed to the plunger and is initially contained within such a chamber. The other end of the ampoule is sealed by a diaphragm which is pressed against a beaded end portion of a cylinder and is sealed thereto by a cup-shaped clip which snaps over the beaded end portion to thereby compress the diaphragm against the end portion. The clip has a peripheral rim about a recessed bottom end which stretches the patient&#39;&#39;s skin to facilitate the injection. According to one aspect of the invention, such an ampoule is designed to perform a subcutaneous injection. According to a further aspect of the invention, such an ampoule is designed to perform an intramuscular injection. According to a still further aspect of the invention, the ampoule includes multiple chambers for premixing a medicament with at least one other medicament and injecting the mixture, either subcutaneously or intramuscularly. Applicators designed to receive and hold the several forms of ampoules and to actuate them as required by their particular forms and functions provide several applicator-ampoule combinations of novel structure and functions.

United States Patent [191 Hurschman et al.

[111 3,797,490 1 Mar. 19, 1974 HYPODERMIC AMPOULE WITH SKIN TENSIONINGCLIP [75] Inventors: Alfred A. Hurschman; Thomas P.

Schiller, both of Streetsboro, Ohio Related U.S. Application Data [62]Division of Ser. No. 114,493, Feb. 11, 1971, Pat. No.

.[52] U.S. Cl 128/218 M, 128/218 DA [51] Int. Cl A61m 5/28 [58] Field ofSearch 128/215, 216, 218 R, 218 P, ,128/218 NV, 218 D, 218 DA, 218 F,220, 272; 206/632 R, 56 R; 215/47, 52

Primary ExaminerRichard A. Gaudet Assistant Examiner-J. C. McGowan AgentE L'ZZTLMPlYS IXL 3119189111.

Pearne l z Gordon [57] ABSTRACT Hypodermic ampoules of thecontained-needle type, and combinations of such ampoules with so-calledapplicators for actuating the ampoules to make injections are disclosed.Each of several ampoule forms has at least one cylindrical,medicament-containing chamber and a plunger closing one end thereof. Ahollow needle is fixed to the plunger and is initially contained withinsuch a chamber. The other end of the ampoule is sealed by a diaphragmwhich is pressed against a beaded end portion of a cylinder and issealed thereto by a cup-shaped clip which snaps over the beaded endportion to thereby compress the diaphragm against the end portion. Theclip has a peripheral rim about a recessed bottom end which stretchesthe patients skin to facilitate the injection. According to one aspectof the invention, such an ampoule is designed to perform a subcutaneousinjection. According to a further aspect of the invention, such anampoule is designed to perform an intramuscular injection. According toa still further aspect of the inven tion, the ampoule includes multiplechambers for premixing a medicament with at least one other medicamentand injecting the mixture, either subcutaneously or intramuscularly.Applicators designed to receive and hold the several forms of ampoulesand to actuate them as required by their particular forms and functionsprovide several applicator-ampoule combinations of novel structure andfunctions.

' 14 Claims, 22 Drawing Figures BACKGROUND OF THE INVENTION Thisinvention relates to disposable hypodermic ampoules that provide achamber containing both a medicament to be injected and the hypodermicneedle through which the injection is made, the injection beingperformed by collapsing or otherwise actuating the device to project thepointed end of the needle through a puncturable wall of the ampoule andthen into the patient while reducing the volume of themedicament-containing chamber to express the medicament through theneedle and into the patient. Such ampoules are referred to herein by thegeneric designation, contained-needle type.

Ampoules of this general character are represented,

for example, by two series of United States patents granted,respectively, to Russell P. Dunmire and to Stanley J. Sarnoff or StanleyJ. Sarnoff et al. The principal ones of those patents to Dunmire are US.Pat. Nos. 2,769,443, 3,094,987, 3,094,988, and 3,236,237, and theprincipal ones of those patents to Sarnoff (or Sarnoff et al are US.Pat. Nos. 2,704,072, 2,832,339, 3,320,955, and 3,396,726. The devices ofthose patents of Dunmire and Sarnoff (or Sarnoff et al.) involve aparticularly advantageous mode of operation in that the medicament isinjected into the patient from the pointed end of the needle as ittravels longitudinally to its maximum depth of penetration, thus distributing the medicament for faster absorption and minimizing discomfort andtrauma sometimes occasioned by injecting all of the medicament in onelocation after the needle has been inserted to the maximum depth. Theyalso greatly reduce the chances for contamination of the medicament orthe needle; they require little or no skill on the part of the user, andeven make self-injectin safe and practical; and they have numerous otherinherent advantages which the art has long recognized. However, none ofthedevices of that generaltype has yet been perfected sufficiently forwidespread use. i

. For inspection purposes after filling, it is important that ampoulesof the contained-needle types disclosed in the Dunmire and Sarnoff (orSarnoff et al.) patents have transparent walls. In order to make thecollapsible walls of the ampoules of the Dunmire patents transparent, ithas been necessary to mold them from synthetic resin materials which,because of their possible reactivity with certain medicaments duringprolonged periods of storage after filling and before use, have limitedthe use of such ampoules. Although the components of such devices couldbe molded of suitably inert natural rubber, that material does not havethe transparency required for inspection after filling and, therefore,cannot be used for many applications.

the forms of devices shown in those parents have involved variousstructural, assembly, operational, and- /or cost problems that havelimited their usefulness and, hence, their commercial acceptance. Forexample, the puncturable end wall of the devices of those patents ofSarnoff (or Sarnoff et al.) are incapable of sealing against the skin ofa patient. as required to avoid loss of medicament by seepage betweenthe ampoule end wall and surface of the skin, particularly in the caseof such devices designed and used for making relatively shallowsubcutaneous injections. When designed as shown in those patents andused as intended for making intramuscular injections, the flow ofmedicament out of the pointed end of the needle begins as soon as theneedle point emerges from the ampoule for penetrating the skin, and suchflow continues until the needle has penetrated to its maximum depth inthe muscle layer. The result is neither a normal subcutaneous injectionnor a normal intramuscular injection but, rather, is a combination ofthe two that has been acceptable only for very limited injectionpurposes. The devices of those Dunmire patents, on the other hand, wereideal for making subcutaneous injections, but, for the same reason asthe devices of the patents of Sarnoff (or Sarnoff et al.), wereincapable of giving a normal intramuscular injection.

Devices have been proposed which are designed for making subcutaneousinjections. One such device, is shown in US. Pat. No. 3,396,726 toSarnoff and includes a cylinder which defines a medicamentcontainingampoule. A piston driven needle is contained in the ampoule and one endof the ampoule is closed by a pierceable diaphragm. The cylinder is onlypartially filled by the medicament so that the needle may be driventhrough the diaphragm and into the muscle prior to ejection of themedicament from the needle. However the disclosed method of performingthe intramuscular injection according to the Sarnoff patent necessitatesthe injection of air into the patient. When an injection is performed byskilled personnel, there is little danger if air is injected into thepatient. Desirably, however, an injection device should be designed sothat an injection may be performed by unskilled personnel such as thepatient himself. Unskilled personnel may inject air into a blood vesseland it is therefore important to provide an ampoule and an injectionprocedure which eliminates this possibility.

As further examples of problems not heretofore solved, some of thedevices of those patents of Sarnoff (or Sarnoff et al.) and of otherprior art, in order to ensure a proper seal between a tubular, glasssidewall of an ampoule and a puncturable diaphragm closing one endthereof, have included diaphragm retaining members that are integralparts of an applicator for actuating the ampoule (e.g., US. Pat. No.2,832,339 to Sarnoff et al. or have included diaphragm retaining membersthat hold the medicament-containing ampoule in operative position withinan applicator (e.g., US. Pat. No. 2,866,458 to l-lein, Jr.). Suchstructures necessitate assembly and filling of an ampoule during theassembly of the ampoule within an applicator. However, it is frequentlydesirable to assemble and fill an ampoule of the contained-needle typeand then ship that ampoule to the user so that the user may install itin an applicator.

A more acceptable solution to the problem of sealing a diaphragm to amedicament-containing cylinder may be found in US. Pat. No. 2,704,073 toJensen. In the Jensen patent, the diaphragm is sealed against one end ofa cylinder by a cup-shaped slip which snaps over a beaded end portion ofthe cylinder to press the diaphragm against the end of the cylinder.This permits an ampoule to be assembled prior to shipment and laterinstalled in an ampoule applicator. However, it provides a relativelylarge, substantially flat, skincontacting surface that is incapable ofsealing against loss of medicament by seepage between that end wall andthe skin.

Moreover, neither the aforementioned Jensen patent nor any of thepreviously mentioned patents of Sarnoff et al. and Hein, Jr. provides apuncturable diaphragm that will permit an ampoule that is substantiallyfull of liquid to be actuated to reduce the liquid chamber volume andforce the needle through the diaphragm without occasionally (-at least)creating a hydraulic lock that either bursts the ampoule or preventsinitial movement of a plunger for causing the needle to puncture thediaphragm and thereby release the liquid for injection. Dunmire U.S.Pat. Nos. 3,094,988 and 3,236,237, which disclose solutions of thelatter problem in the case of molded plastic ampoules, fail to providesolutions for the other problems described above.

The applicator disclosed in U.S. Pat. No. 3,236,237 to- Dunmire involvesa special endwall construction that cooperates with the specialdiaphragm of Dunmire U.S. Pat. No. 3,094,988 to perform the desirablefunctions set forth therein. However, in many instances it is desirableor necessary to perform an injection without employing an applicator.Furthermore, it may be desirable to perform an injection with anapplicator different than the particular kind set forth in that patent,so that the advantages afforded by the teachings of the patent must belost or achieved in some other manner.

A number of drug compounds, including some antibiotics, some vaccines,and several other injectable products, require that an active ingredient(usually in a powder form) be mixed with an injection vehicle (usuallywater) shortly before administration. One widely accepted procedure formixing powder and liquid medicament components is to provide them inseparate vials, each having its own rubber stopper closing its outletopening. The liquid is withdrawn from its vial by a needle and syringeand is then injected into the vial containing the powder. The thus mixedliquid and powder in the latter vial, after shaking it where required,are withdrawn as a dispersion by the same neetile. and syringe, and theinjection is effected therewith in a conventional manner.

Attempts have been made to provide a multicompartment vial whereinliquid and solid components to be mixed prior to injection areseparately contained in a manner that permits mixing them within thecommon vial. For example, U.S. Pat. No. 2,495,942 to W. A. Nosekprovides an outer container having an inner container mounted therein.The outer container contains a liquid medicament and the inner containercontains a solid medicament. The inner container is releasably sealed toa stopper which closes both containers. By depressing the stopper, theinner container is released so that its solid contents may mix with theliquid. The mixture is then withdrawn by piercing the stopper with theneedle of a hypodermic syringe. Such an arrangement, however, is notreadily applicable to the contained-needle type of hypodermic ampoulesto which the present invention relates, apart from other objectionsthereto.

Another proposal for providing a multichamber container is set forth inU.S. Pat. No. 3,342,180 to Sandhage et al., dated Sept. 19, 1967. Inthat patent, the patentees provide a vial which is separated into twochambers by a plunger. Powder is provided in a lower chamber and liquidis provided in the upper chamber. The plunger is provided with a one-waycheck valve so that, upon retraction of the plunger, the liquid isforced through the valve and into the compartment containing the powder.The vial is provided with an external needle at its lower end so thatthe mixed medicament may be injected into the patient. Again, apart fromother objections thereto, such an arrangement is not readily applicableto the contained-needle type of hypodermic ampoules to which the presentinvention relates.

As a result of the foregoing problems, and numerous others, priorhypodermic ampoules of the containedneedle type, to which the presentinvention relates, have all been subject to severe limitations on theirpractical utility, and their uses have been restricted accordingly. Thepresent invention is directed to the provision of a basic ampoule designof the containedneedle type that is adaptable for making bothsubcutaneous and intramuscular injections, either of a containedpremixed medicament or of two or more separated medicament componentsthat are mixed in the ampoule itself. A major objective is to achieveall of this 1. with a maximum utilization of basic parts of both theampoules and applicators therefor,

2. with a minimum variation in the techniques of assembling, filling,and using the ampoules, and

3. while overcoming or avoiding the many problems that have heretoforeprevented general use of the desirable, contained-needle type ofinjection device.

SUMMARY OF THE INVENTION In its simplest form,-this invention provides adisposable ampoule of the contained-needle type having a rigid,cylindrical sidewall, an actuating, needlecarrying plunger in one endthereof, and an improved skin-engaging, puncturable, endwall assembly atits opposite end that is suitable for use, also, in the other forms ofthe invention disclosed herein and for use with a variety of applicatorsor without employing any applicator. The improved, puncturable, endwallassembly includes the main features of the puncturable diaphragm ofDunmire U.S. Pat. No. 3,094,988 and a novel clip for fastening thediaphragm to the cylindrical sidewall.

The clip according to this invention is cup-shaped and has a cylindricalsidewall provided with an annular groove which snaps over a radiallyextending, circumferential bead adjacent the end of the cylinder. Thebottom of the clip has a central opening therein for receiving acentral, needle-guiding, gland portion of the puncturable diaphragm. Theexternal bottom surface of the clip is concave and tapers inwardly froman outer rim portion to the central opening so that, upon engagement ofthe clip with the skin to effect an injection, the skin is stretched toresist indentation by the gland and produce a more reliable seal betweenthe gland and the skin, while urging the gland axially ina slidableplunger carrying a needle with a longer cannula. In this case, thecylinder is only partially filled with medicament. Prior to aninjection, the plunger is partially depressed by pushing it toward thediaphragm so that the needle projects through and beyond the diaphragmand so that air within the ampoule is expelled prior to initiating theinjection. The projecting end of the needle is then pushed through theskin and fascia layers and into the muscle of the patient, and theplunger is completely depressed to inject the medicament as the needletravels further into the muscle. A removable protective shield for thepartially advanced needle is preferably provided as an attachment to thepuncturable clip and diaphragm assembly and is removed just prior tomaking the actual injection. Otherwise, this form of the inventiondiffers from the first described form primarily in the lengths of thecylindrical sidewall and needle cannula.

This invention also provides a multichamber, hypodermic device whichincludes first and second coaxially disposed cylinders. The cylindersrespectively provide first and second, medicament-containing chambers,the adjacent ends of which are separated by a first, puncturable,piston-like diaphragm. This first diaphragm extends across and aroundthe end of the first cylinder to close and seal the same and is slidablymounted in the adjacent end of the second cylinder to close andseparately seal the same. These two seals are exposed to and separatedby the ambient atmosphere so as to aovid liquid seepage from one chamberinto the other. The other end of the first cylinder slidably carries aplunger. A hypodermic needle is mounted on the plunger with its pointedend extending axially toward a pierceable, central portion of the firstdiaphragm. The other end of the second cylinder is closed and sealed bythe above described, puncturable, clip and diaphragm assembly having itspierceable portion also axially aligned with the pointed end of theneedle.

The first chamber is partially filled with a first medicament, usuallyin powder form, and the excess space therein is preferably partiallyevacuated. The second chamber is filled with a second, liquid medicamentor vehicle for the first medicament. These medicament components aremixed by partially depressing the plunger so that the pointed end of theneedle cannula pierces thefirst diaphragm. The partial vacuum in theexcess space in the first chamber facilitates the flow of liquid fromthe second chamber through the needle and into the first chamber as thefirst diaphragm moves toward and into engagement with the seconddiaphragm, thus mixing the two medicaments. When the second chamber isexhausted and its volume reduced essentially to zero in this manner, aninjection may be effected by pressing the puncturable clip and diaphragmassembly against the skin of a patient and further depressing theplunger to the end of its stroke.

This invention also provides similar multichamber devices like the onelast described but with the similar provision in the second cylinder ofone or more additional, coaxially disposed chambers containingadditional, liquid medicament components to be sequentially mixed in alike manner with the first two components prior to making the actualinjection.

A basic applicator design is provided for receiving and actuating eachof the several ampoule forms to perfonn the particular injections forwhich each is designed.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of asingle chamber ampoule according to this invention.

FIG. 2 is an enlarged, cross-sectional view, the plane of the sectionbeing indicated by the line 2-2 in FIG.

FIGS. 3 and 4 are cross-sectional views similar to FIG. 2, but showingthe ampoule in an applicator and showing component parts of the ampouleand applicator in positions attained during an injection.

FIG, 5 is a cross-sectional view of an ampoule which is adapted toperform an intramuscular injection according to a further aspect of thisinvention.

FIG. 6 is a cross-sectional view similar to FIG. 5, but showingcomponents parts of the ampoule in positions attained prior to aninjection.

FIG. 7 is a cross-sectional view similar to FIG. 6, but showing theampoule mounted in an applicator and ready for an injection..

FIG. 8 is a cross-sectional view similar to FIG. 7, but showing theampoule in a position. performing an injection.

FIG. 9 is a perspective view of a multichamber hypodermic ampouleaccording to a further aspect of this invention.

FIG. 10 is a cross-sectional view of the ampoule of FIG. 9, the plane ofthe section being indicated by the line Ill-10 in FIG. 9.

FIGS. 11, 12, and 13 are cross-sectional views similar to FIG. 10, butshowing component parts of the ampoule in positions attained afterinitiating a mixing operation, completion of the mixing operation, andcompletion of an injection operation, respectively.

FIG. 14 is a cross-sectional view of a multichamber hypodermic ampouleaccording to a further aspect of this invention.

FIG. 15 is a cross-sectional view of a multichamber hypodermic ampouleaccording to a still further aspect of this invention.

FIGS. 16 and 17 are cross-sectional views illustrating the componentparts of the ampoule of FIG. 15 in positions attained at the completionof a mixing operation and after further actuation to ready it for makingan injection, respectively.

FIG. 18 is a perspective view of a needle which may be employed incombination with devices according to this invention.

FIGS. 19 and 20 illustrate progressive filling and assembly operationsto produce the ampoule illustrated in FIGS. 9 through 13.

FIG. 21 is a fragmentary perspective view of an ampoule retaining clipprovided in the applicators illustrated in FIGS. 7, 8, and 17.

FIG. 22 is a bottom end view of an ampoule mounted in the applicatorillustrated in FIGS. 7, 8, and 17.

DETAILED DESCRIPTION OF THE INVENTION Referring now to the drawings, andparticularly to FIGS. 1 through 4, a single chamber ampoule 10 isillustrated. The ampoule 10 is adapted to perform a sub cutaneousinjection and includes a cylinder 11. The cylinder 11 is preferably madefrom glass tubing an has a radially extending annular bead 12 at oneend. That end of the cylinder 11 is closed by a diaphragm 13 which ispressed against it by a plastic clip 14. The clip 14 is cup-shaped andhas an inner annular groove 15 in its cylindrical sidewall which snapsover the bead 12. The clip 14 also includes a bottom wall 14a having acentral aperture 14b therethrough. the bottom wall 14a has a concaveoutside surface which includes an outer rim 14c and which tapersupwardly toward the aperture 14b.

The diaphragm 13 is preferably molded from rubber and is shaped tofunction in accordance with the teachings of US. Pat. No. 3,094,988 toDunmire. It includes an outer, annular portion 16, a thick, elongated,centrally located, needle guiding and liquid sealing gland 17, and arelatively thin, flexible, corrugated, intermediate portion 18connecting the gland and the outer portion to permit relative axialmovement therebetween. The gland extends through the aperture 14b in theclip 14. An. axial needle passage 19 may extend into the upper end ofthe gland from the inside and terminates short of the opposite, lowerend of the gland to form a thin, easily puncturable wall 20 closing thebottom of the passage. Alternatively, this needle passage may be omittedwhen molding the diaphragm and, in effect, be formed by partial piercingof the gland by the needle during assembly of the ampoule.

The other end of the cylinder 11 is closed by a plunger 21 which is alsopreferably molded from rubber and formed to have a sliding interferencefit with the inner sidewall of the cylinder 11. The plunger 21,diaphragm l3, and cylinder 11, together, define a chamber 22 which issubstantially filled with'a liquid medicament.

Entirely enclosed within the chamber 22 is a hypodermic needle23 (FIG.18) which is preferably of the type disclosed in US. Pat. No. 3,173,200to Dunmire et al. The illustrated circular base 24 at the butt end ofthe needle 23 is mounted on the plunger 21 so that the needle is insubstantial axial alignment with the cylinder 11 and has a pointed end25 projecting downwardly and received within the axial needle passage 19of the diaphragm gland 17 in position to be forced through the thin wall20 of the gland. Mounting of the needle base 24 on the plunger 21 iseffected by snapping the peripheral edge of the needle base under anannular lip 26 that is an integral part of the plunger. Flow into thebutt end of the needle from the chamber 22 occurs through an opening 27in the cannula wall adjacent the base 24 of the needle.

An injection is effected by first pressing the diaphragm gland 17 firmlyagainst the patients skin S, thus indenting the skin until the rim 14cof the bottom of the clip 14 also firmly engages the patients skin. Asmay be seen in FIGS. 3 and 4, when the clip 14 and the gland 17,together, firmly engage the skin S, the skin is stretched and domesupwardly to thereby seal it more tightly against the gland while forcingthe gland axially inwardly toward the pointed end 25 of the needle 23.Force is then applied to the upper end of the plunger 21 (eithermanually or by means of an ampoule applicator) to move it downwardlytoward the diaphragm 13 so that the needle 23 penetrates the gland wall20 (see FIG. 3) and enters the patients skin. As the plunger isdepressed in this manner, the liquid medicament in the chamber 22 isforced through the opening 27 in the upper end of the needle, throughthe needle cannula, and into the subcutaneous tissue of the patient. Byreason of the simultaneous upward pressure of the skin S on the gland l7and the outward flexibility of the corrugated diaphragm portion 18, theneedle is easily driven through the gland wall 20 before hydraulicpressure within the ampoule can block movement of the plunger. Also, theseal between the gland l7 and the skin S virtually prevents any seepageof medicament therebetween as the point of the needle of I-Iurschman,Ser. No. 114,423, filed Feb. 11, 1971,

now US. Pat. No. 3,729,003, issued Aug. 24, 1973. A lower end portion 28of that applicator is illustrated in FIGS. 3 and 4. The ampoule 10 ismounted within the portion 28 by a bayonet-type connection between theampoule 10 and the portion 28. As is more fully set forth in theapplication ofHurschman, this connection is effected by providingaxially extending, diametrically opposed slots (not shown herein)through an inwardly extending flange portion 29 of the applicator and byproviding cooperating, radially extending lugs 14d on the clip 14. Thelugs 14d are received within the slots and enter channels 29a and 29bwhich extend in a clockwise direction and taper radially inwardly towardthe inner cylindrical sidewall of the portion 28. The ampoule may beremovably retained in the applicator by inserting the lugs 14d into theslots and turning the clip 14 in a clockwise direction until the lugs14d frictionally engage the inwardly tapering sidewalls of the channels29a and 29b. The means to apply force to the plunger 21 includes aspring biased force applying head 28a which is held in a retractedposition illustrated in FIG. 3 by detent means (not shown). When thedetent means is released, the force applying head drives the plunger 21to the position illustrated in FIG. 4.

Referring now to FIGS. 5 through 8, a single chamber ampoule 30 isillustrated. The ampoule 30 is adapted to perform an intramuscularinjection and includes a cylinder 31 which is preferably made from glasstubing. One end of the cylinder 31 is provided with a radially extendingannular head 32, and that end of the cylinder is closed by a rubberdiaphragm 33 that may be identical with the diaphragm 13 of FIGS. 2-4.The diaphragm 33 is pressed and held against the bead 32 by a clip 34similar to the clip 14 of FIGS. 2-4. The other end of the cylinder 31 isclosed by a rubber plunger 41 having an enlarged portion 42 which formsa sliding interference fit with the inner sidewall of the cylinder 31.The plunger 41 is provided with an axially extending reduced upperportion 43 which initially extends beyond the cylinder 31.

The plunger 41, diaphragm 33, and cylinder 31, together, define achamber 44 which is partially filled with a liquid medicament. A spaceSp (FIG. is provided between the level of the medicament and the initialposition of the plunger, and the axial extend of the portion 43 of theplunger 41 corresponds to the axial extent of the space Sp.

Contained within the chamber 44 is a needle 45 which may be identicalwith the needle 23 illustrated in FIGS. 2-4 and 18 except for having alonger cannula and is disposed and mounted in the chamber similarly tothe arrangement of FIGS. 2-4. A needle guard 46 is removably fixed tothe clip 34 and extends axially therefrom. The needle guard 46 ispreferably of transparent plastic, is cup-shaped, and has an open mouthwhich forms an interference fit with an annular, axially projectingshoulder portion 47 of the clip 34. For purposes which will hereinafterbecome apparent, the guard 46 so provided with a knurled bottom rib 48and has an axial extent which is greater than the space Sp.

To ensure an intramuscular type injection, the needle 45 must passthrough the skin, underlying surface layers of fat, and the fascia layerand enter the muscle prior to medicament flow through the needle.Therefore, the chamber 44 is designed so that its volume is greater thanthe volume of medicament contained therein. Prior to effecting aninjection, the plunger 41 is depressed until the upper end of theportion 43 is level with the top of the cylinder 31, at which point thelower end of the plunger contacts thev surface of the liquid in thechamber 44. During this depression operation, the needle 45 pierces thediaphragm 33 and the air or gas in the space Sp is substantially allexpelled through the needle. This operation is most convenientlyperformed by placing the needle guard 46 on a flat surface and pressingthe plunger portion 43 downwardly until the ampoule 30achieves thecondition illustrated in FIG. 6. If desired, the plunger may bedepressed in this manner until the appearance of a drop of medicament atthe point of the needle (visible through the transparent sidewall of theneedle guard 46) indicates the elimination of substantially all air orgas from the chamber 44. This operation projects the needle 45 apredetermined distance beyond the diaphragm 33, which distancesubstantially corresponds to the normal maximum depth of the musclebeneath the skin of the patient, and air or gas in the chamber 44 issubstantially fully expelled in the process.

After achieving the condition illustrated in FIG. 6, an intramuscularinjection may be effected by manually removing the needle guard 46,inserting the needle through the skin, fatty layer, and fascia layer andinto the muscle, and then completely depressing the plunger 41. Apreferred method of effecting an injection, however, is to employ anapplicator. As fragmentarily shown herein, such an applicator includes aspringbiased plunger 50 (FIGS. 7 and 8) mounted within a casing 51. Anapplicator adapted to perform an intramuscular injection includes anelongated, metal, bellshaped mouth portion 52 which is provided withdiametrically opposed inner spring clips 53 or the like (see FIG. 21)which are spot welded to the inner sidewall of the portion 52. The clips53 retain the ampoule diaphragm clip 34 in the position illustrated inFIG. 7, so

that the partially advanced needle 45 is initially recessed in theapplicator. With the needle guard attached, the ampoule 30 is mountedwithin the applicator by inserting a pair of diametrically opposed lugs34a provided on the clip 34 into a cooperating pair of slots 52a (FIG.22 which extend axially through a radially inwardly extending flange521). This operation is performed by grasping the knurled bottom rib 48on the needle guard 46. The ampoule is pushed upwardly into the casing51 until the lugs 34a are above the level of the spring clips and isthenrotated until the lugs 34a rest on the clips 53 (see FIG. 7). It isdesirable to remove the guard 46 after the ampoule 30 is mounted in theapplicator to prevent contamination of the needle. The needle guard isremoved by pulling one portion of the rib 48 downwardly while pushing adiametrically opposed portion of the rib upwardly since an axial forceapplied to the rib may disengage the lugs from their retaining springclips. After the needle guard is removed, the mouth 52 of the applicatoris placed against the skin of the patient and the plunger is fired. Theapplicator spring clips 53 are designed so that they release the ampoulediaphragm clip 34 prior to movement of the plunger 41 relative to theampoule cylinder 31. To this end, the springs are designedso that theforce required to drive the lugs 34a from their retained position isless than the force required to move the plunger 42 relative to thecylinder 31. In this manner, the needle 45'is driven into the muscle M(FIG. 8) prior to injection of the medicament. After the needle 45enters the muscle, the plunger 41 again moves toward the diaphragm 33 toperform the injection by expressing the medicament through the needle 45as it is driven fur ther into the muscle M. The injection is completewhen the plunger engages the diaphragm.

Referring now to FIGS. 9 through 13 of the drawings, a multichamberampoule 1.10 is illustrated. The ampoule is adapted to perform asubcutaneous injection and includes a first cylinder 111 and a secondcylinder 112 of larger diameter, both being preferably made from glasstubing. One end of the first cylinder 1 11 has a radially extendingannular bead 1 13 which is received within an annular groove 114provided in a first diaphragm 115. The first diaphragm 115 is preferablymade from rubber and is received with an interference fit within one endof the second cylinder 112. This radially compresses this diaphragm andcauses it to more tightly embrace the cylinder bead 113.

The other end of the first cylinder 11] is closed by a rubber plunger 116 which, together with the first cylinder 111 and the first diaphragm115, defines a first chamber 117. The plunger 116 is preferably made ofrubber and has an interference fit in the first cylinder.

Entirely enclosed within the first chamber 117 is a hypodermic needle118 which may be identical with the needle 23 illustrated in FIGS. 24and 18 except for interference fit between the diaphragm 115 and theinner sidewall of the cylinder 112 aids in sealing the bead 113 withinthe annular groove 114. Friction between the plunger 1 16 and wall ofthe cylinder 111 and resistance of the diaphragm 115 to penetration bythe needle 118, of course, prevent the plunger 116 from prematurelymoving toward the diaphragm 115.

The other end of the second cylinder 112 is closed by a second diaphragm124 and a clip 125 constructed and operating like the previouslydescribed similar diaphragm and clip of FIGS. 24, the diaphragmcomprising portions 127, 128, and 129 corresponding to portions 16, 17,and 18 of the diaphragm of FIGS. 2-4 and having a similar needlereceiving passage 130 ending in a puncturable wall 131 closing thebottom of the passage.

The first diaphragm 115, second diaphragm 124, and

The liquid medicament in the second chamber is mixed with the solidpowder medicament in the first chamber prior to injection in a mannerwhich will now be explained. The plunger 1 16 is pushed axially towardthe first diaphragm 115 until the needle 118 pierces this diaphragm andprovides communication through the needle between the second chamber 132and the first chamber 117, as shown in FIG. 11. Once communication isestablished between these chambers, the liquid is drawn upwardly intothe first chamber by downward movement of the cylinder 11] and firstdiaphragm 115, together, into engagement with the second diaphragm 124,as shown in FIG. 12. At this stage, the pointed end of the needle 118,which previously pierced the first diaphragm 115, has entered the gland128 of the diaphragm 124.

To ensure that the pointed end of the needle will not be initiallyextended too far beyond the first diaphragm 115 after it pierces thatdiaphragm, the plunger 116 is provided with a centrally raised portion140 which extends beyond the end of the cylinder 11 1 when the ampouleis initially assembled. The raised portion 140, therefore, extendsbeyond the end of the cylinder 111 for a distance which substantiallycorresponds to the thickness of the portion of the diaphragm 115 to bepierced plus the desired extension of the needle beyond the diaphragm115 during the mixing operation. To perform the penetration operation,therefore, the raised portion 140 is depressed until its upper or outerend is flush with the top mouth of the cylinder 111, as illustrated inFIGS. 11 and 12.

When the ampoule 110 is in the condition illustrated in FIG. 12 and theampoule has been inverted several times or vigorously shaken as reliablemixing of the medicament components may require (generally notnecessary), the ampoule is in a condition suitable for making asubcutaneous injection. To perform the injection, the diaphragm 124 isplaced adjacent the patients skin 'and the plunger is fully depresseduntil it assumes the position illustrated in FIG. 13. During the plungerdepressing step, the needle penetrates the wall 131, and fluid isexhausted from the first chamber through the needle opening adjacent theplunger 116 and through the opening in the end of the needle as theneedle penetrates the skin and subcutaneous fat of the patient.

Referring now to FIG. 14, an ampoule is illustrated. Theampoule 150 issuited for performing an injection requiring the premixing of two ormore liquid medicaments with each other or with each other and with asolid medicament. The ampoule 150 includes a first cylinder 151 which ispreferably made from glass and which has a beaded rim portion 152 at itslower end. The rim portion 152 is received within an annular groove 153which is provided in a first diaphragm 154. The diaphragm 154 closes oneend of the cylinder 151, and the other end of the cylinder 151 is closedby a plunger 155. A needle 156 similar to the needles 23 and 118 (exceptfor cannula length) is mounted on the plunger similarly to thearrangement of FIGS. 2-4. A pointed end 159 of the needle 156 isreceived within a passage 160 in the first diaphragm 154. The plunger155, cylinger 151, and the diaphragm 154, together, define a firstchamber 161. As will be hereinafter explained in greater detail, thechamber 161 is partially evacuated during the assembly operation and isat least partially filled with a liquid or powdered medicament 162.

The first diaphragm 154 is slidably received within a second cylinder163. The second cylinder 163 has its upper end closed by the firstdiaphragm 154 and has its lower end closed by a second diaphragm 164 anda clip 165 constructed and operating like the previously describedsimilar diaphragm and clip of FIGS. 2-4.

Intermediate diaphragms 167 and 168 are provided in the cylinder 163.The intermediate diaphragms 167 and 168, the diaphragms 154 and 164, andthe cylinder 163, together, define second, third, and fourth chambers169, 170, and 171, respectively. The chambers 169, 170, and 171 arefilled with different liquid medicaments.

The medicaments contained in the chambers 169-171 are mixed together,and the mixture is in turn mixed with the powder 162 in the followingmanner. The plunger 155 is pushed downwardly until the needle 156pierces the first diaphragm 154 to provide fluid communication betweenthe chamber 169 and the chamber 161. The fluid in the chamber 169 isdrawn through the hollow needle 156 and into the chamber 161. After theliquid in the chamber 169 is exhausted in this manner, the diaphragm 154contacts the diaphragm 167 and the pointed end 159 of the needle entersa passage 172 in the diaphragm 167. Further pressure on the plunger 155causes the needle 156 to pierce the diaphragm 167 to thereby draw liquidfrom the the chamber into the chamber 161 and move the diaphragm 167against the diaphragm 168. The pointed end 159 of the needle 156 thenenters a passage 173 in the diaphragm 168 and further pressure on theplunger 155 drives the needle 156 through the diaphragm 168 to therebydraw liquid from the chamber 171. After the liquid in the chamber 171 isexhausted, the diaphragm 168 contacts the diaphragm 164 and the pointedend of the needle is received within a passage 174 provided in thediaphragm 164.

After the several liquids are mixed with each other and with thematerial 162 in the chamber 161, the ampoule 150 is in a condition toperform an injection. This injection is performed by placing thediaphragm 164 against the skin of the patient and by depressing theplunger 155 until the plunger 155 contacts the diaphragm 154. It shouldbe appreciated that any number of liquids may be mixed in this mannerwith or without a powdered medicament, after which the ampoule, with orwithout an applicator of the kind partially shown in FIGS. 3 and 4, maybe used to make a subcutaneous injection in the general mannerpreviously described.

Referring now to FIGS. 15, 16, and 17, an ampoule 180 is illustrated,The ampoule 180 may be employed to mix liquid and powdered medicamentsprior to an injection, and may be employed to effect an intramuscularrather than subcutaneous injection. The ampoule 180 is generally similarto the ampoule 110 in that it includes a first cylinder 181 which isclosed at one end by a rubber plunger 182 and is closed at the other endby a first diaphragm 183. A needle 184 is fixed to the plunger 182 inthe same manner previously described, and the diaphragm 183 is slidablyreceived in a second cylinder 185. The second cylinder 185 is closed atits lower endby a second diaphragm 186 and a clip 187 constructed andoperating like the previously described similar diaphragm and clip ofFIGS; 2-4. A needle guard 188 similar to the needle guard 46 of FIGS.and 6 is removably fixed to the clip 187 and extends axially therefromas previously described with reference to the latter figures of thedrawings.

The first cylinder 181, diaphragm 183, and plunger 182, together, form afirst chamber 190 which is evacuated and partially filled with apowdered medicament 191. The second cylinder 185 and diaphragms 183 and186, together, form a second chamber 192 which is filled with a liquidmedicament 193.

The medicaments 191 and 193 are mixed in a manner similar to the mixingprocedure set forth with regard to the ampoule of FIGS. 9-13. Theplunger 182 ispushed axially until the needle 184 pierces the diaphragm183 and provides liquid communication between the chambers 190 and 192.When such communication is established, the diaphragm 183 moves intoengagement with the diaphragm 186, and the parts of the ampoule 180assume the positions illustrated in FIG. 16.

To ensure an intramuscular type injection, the needle 184 mustpassthrough the skin and the surface layers of fat and enter the muscleprior to medicament flow through the needle. Therefore, the chamber 190is designed so that its volume is greater than the total volume ofmedicament to be contained therein. Thus, as is illustrated in FIG. 16,there is a space Sp between the liquid level and the plunger 182 whenthe diaphragms 183 and 186 are drawn together. Prior to effecting aninjection, the plunger 182 is further depressed until the plunger 182contacts the surface of the liquid in the chamber 190. This operationprojects the needle 184 a predetermined distance beyond the diaphragm186, which distance substantially corresponds to the normal maximumdepth of the muscle beneath the skin of the patient, and air or gas inthe chamber 190 is substantially fully expelled in the process aspreviously described with reference to FIGS. 5-8.

An injection may then be performed by removing the needle guard 188 andmanually applying the ampoule 180 against the skin of the patient sothat the needle 184 penetrates the skin and enters the muscle. Afterthis operation, the plunger 182 is completely depressed to inject themedicament into the muscle. Desirably, however, the injection isperformed by an applicator which may generally correspond to theapplicator.

dered medicament. While subjected to the vacuum, the

first diaphragm is applied to the mouth of the cylinder. Thereafter, thesecond cylinder 112 is applied to the diaphragm 115, as illustrated inFIG. 20. The second cylinder 112 is then filled with a liquidmedicament, and the remaining components are assembled to provide theampoule shown in FIGS. 9 to 13.

The invention is not restricted to the slavish imitation of each andevery detail set forth above. Obviously, hypodermic devices may beprovided which change, eliminate or add certain specific details withoutdeparting from the scope of the invention.

What is claimed is: t

1. In a unitary hypodermic device of the containedneedle type comprisinga 7 closed medicamentcontaining cylindrical glass ampoule having apierceable wall at one end thereof, a hypodermic needle having a pointeddischarge end disposed in the ampoule for movement to pierce and projectthrough said pierceable wall, and means for moving said needle throughsaid pierceable wall while expressing medicament from the ampouletherethrough; the improvement in which said ampoule has an outercircumferentially extending bead adjacent the pierceable wall endthereof, and said pierceable wall includes a relatively rigid annularouter portion frictionally retained by said bead and having an externalsurface configured to provide an annular, skinengaging rim surrounding aconcavely recessed surface portion that defines a central openingthereon and a cylindrical sidewall having an internal circumferentialgroove for receiving said bead and locking said outer portion to saidampoule, said cylindrical sidewall also including an end portion beyondsaid internal groove that snugly engages said cylinder about itscircumference inwardly of the bead thereon, and said. bead havingopposite side portions that slope differently relative to the axis ofsaid cylinder to facilitate forcing said end portion of said outerportion over said bead when ap plying said outer portion to the cylinderand to render removal thereof by reverse movement more difficult; and aseparate relatively flexible pierceable inner diaphragm portion forclosing the end of said ampoule and held in position by said outerportion, said diaphragm portion having a central gland projectingoutwardly through said central opening in said outer portion andembracing the pointed discharge end of said needle, said annular rim andprojecting gland being axially related to be pressed, together, againstthe skin of the patient to tense the skin, within the rim for increasingthe resistance of the skin topressure from the gland and moreeffectively sealing the gland against the skin while urging the glandinwardly against the pointed end of the needle to facilitate piercing ofthe gland and the skin upon actuation of said needle-moving means.

2. A hypodermic ampoule according to claim 1 in which said cylindricalsidewall of said outer portion is sufficiently resistant to elasticdeformation to substantially prevent its removal without breaking saidampoule.

3. A multichamber ampoule for mixing and discharging medicaments,comprising a first cylinder, a first diaphragm sealed to and closing oneend of said first cylinder, a plunger slidably disposed in the other endof said first cylinder to provide a first chamber between said plungerand first diaphragm, a hollow needle disposed in said first chamber formovement with said plunger toward said first diaphragm and having anopen end adjacent said plunger and an opposite pointed discharge endadjacent said first diaphragm, and a powder medicament in said firstchamber; a second cylinder axially aligned with said first cylinder andhaving one end closed by insertion of said first diaphragm therein witha peripheral portion of the first diaphragm in axial sliding engagementwith the inner surface thereof, a second diaphragm closing the other endof said second cylinder, said first and second diaphragms and secondcylinder, together, defining a second chamber, and a fluid medicament insaid second chamber; whereby said fluid and solid medicaments may bemixed preparatory to discharge thereof by first moving said plunger andneedle sufficiently toward said first diaphragm to project the pointedend of the needle through said first diaphragm to establishcommunication between the two chambers and by then moving said firstcylinder, first diaphragm, plunger, and needle as a unit toward saidsecond diaphragm to progressively reduce the volume of said secondchamber substantially to zero and thereby express said liquid medicamentthrough the needle into the first chamber while bringing said first andsecond diaphragms substantially into engagement and disposing thepointed end of said needle in position to project the needle throughsaid second diaphragm upon further movement of said plunger toward saidfirst and second diaphragms the improvement in which said seconddiaphragm comprises a pierceable wall having a relatively rigid,annular, outer portion having an external surface configured to providean annular, skin-engaging rim surround a concavely recessed surfaceportion that defines a central opening therein and a relativelyflexible, pierceable, inner diaphragm portion having a central glandprojecting outwardly through said central opening and embracing thepointed discharge end of said needle.

4. A multichamber hypodermic ampoule according to claim 3, wherein theouter diameter of said first cylinder is less than the inner diameter ofsaid second cylinder.

5. A multichamber hypodermic ampoule according to claim 3, wherein thevolume of said first chamber is substantially equal to the volume ofsaid second chamher.-

6. A multichamber hypodermic ampoule according to claim 3, wherein thevolume of said first chamber sufficiently exceeds the volume of saidsecond chamber so that the volume of the two medicaments in said firstchamber after mixing the medicaments therein is substantially less thanthe remaining volume of said first chamber, whereby, prior to expellingthe mixed contents of the first chamber, said plunger may be furtheradvanced toward said first and second diaphragms to extend a portion ofthe length of said needle through and beyond said second diaphragm in anexposed condition for projection into a patient to the depth of muscletissue to be injected, and said plunger may then be moved further towardsaid first and second diaphragms to progressively expel the mixedcontents of said first chamber through said needle and into said muscletissue while further advancing said needle into said muscle tissue.

7. A multichamber hypodermic ampoule according to claim 3, in which atleast one additional diaphragm is disposed in said second chamberbetween said first and second diaphragms so as to divide said secondchamber into a plurality of smaller chambers, and a correspondingplurality of different liquid medicaments respectively substantiallyfill said smaller chambers, whereby each of said liquid medicaments, oneafter another, may be caused to flow through said needle into said firstchamber by progressive movement of said first diaphragm, first cylinder,plunger, and needle, as a unit, to bring all of said diaphragmssubstantially into engagement with one another.

8. A hypodermic ampoule comprising a cylinder; a plunger closing one endof the cylinder with a sliding seal; a pierceable diaphragm closing theother end of the cylinder to provide a medicament chamber therein;

a hypodermic needle disposed in said chamber and extending axiallythereof for movement with said plunger toward said diaphragm, saidneedle having an opening from the chamber into the needle at one endthereof adjacent said plunger and an opposite, pointed, discharge end;and a clip secured to said other end of said cylinder and having abottom portion pressing said diaphragm into sealed engagement with thatend of the cylinder; said diaphragm having an outwardly extendingcentral gland portion embracing the pointed end of the needle, and saidbottom portion of said clip having an external surface configured toprovide an annular, skin-engaging rim surrounding a concavely recessedsurface portion defining a central opening therein through which saiddiaphragm gland projects so that said clip rim and projecting gland maybe pressed, together, against the skin of a patient to tension the skinwithin the clip rim, whereby the skin firmly engages the gland to urgeit inwardly and facilitate penetration of the gland and skin by theneedle upon inward move ment of said plunger to inject medicamentthrough the needle and into the patient, a liquid medicament partiallyfilling said chamber so as to leave an initial space between saidplunger and the medicament when the ampoule is vertically disposed withthe plunger end thereof uppermost, whereby the plunger may be movedinwardly to project the needle through and beyond said diaphragm glandprior to expressing liquid medicament through the needle, and whereinsaid plunger has a portion extending axially beyond the plunger end ofsaid cylinder for a distance substantially corresponding to the lengthof said space axially of the cylinder.

9. A hypodermic ampoule according to claim 8, including a cup-shapedneedle guard removably secured to said clip and having a bottom portionspaced from said gland an axial distance substantially corresponding tothe axial length of said initial space between said plunger andmedicament.

10. A hypodermic ampoule according to claim 8, wherein said plunger anddiaphragm are rubber and said cylinder is rigid and substantiallytransparent.

11. A hypodermic ampoule according to claim 8 in which said cylinder hasan outer, circumferentially extending bead adjacent the diaphragm endthereof, and said clip is cup-shaped with a cylindrical sidewallembracing said bead and the adjacent end portion of the cylinder forsecuring the clip and said diaphragm to the cylinder.

12. A hypodermic ampoule according to claim 8 in which said cylinder isformed of glass and has an outer, circumferentially extending beadadjacent the diaphragm end thereof, said clip being cup-shaped with agenerally cylindrical sidewall embracing said bead and the adjacent endportion of the cylinder, and said cylindrical sidewall of the cliphaving an internal, circumferential groove receiving said bead of saidcylinder and locking the clip against removal.

13. in a hypodermic injection assembly:

a. a contained-needle type of hypodermic ampoule comprising a cylinder,a puncturable diaphragm closing and sealing one end of said cylinder, aslid able plunger in the opposite end of said cylinder and spaced fromsaid diaphragm to provide a chamber therebetween, a liquid medicament insaid chamber, and a hypodermic needle disposed in said chamber formovement by said plunger to a preinjection position in which a dischargeend portion of the needle has pierced and extends beyond said diaphragmin an exposed condition and thereafter to transmit medicament from saidchamber into a patient receiving an injection while moving furtherthrough said diaphragm, the volume of medicament in said chamber beingsubstantially less than the initial volume of said chamber to permitmovement of the plunger to project the needle to said preinjectionposition before expressing medicament from the chamber through theneedle, said diaphragm comprising a pierceable wall having a relativelyrigid, annular, outer portion having an external surface configured toprovide an annular, skin-engaging rim surrounding a concavely recessedsurface portion that defines a central opening therein and a relativelyflexible, pierceable, inner diaphragm portion having a central glandprojecting outwardly through said central opening and embracing thedischarge end of said needle; and said ampoule including radiallyprojecting abutments spaced about its periphery;

b. an applicator for actuating said ampoule to perform an injectionafter the needle has been projected to its preinjection position, saidapplicator comprising a housing having an open end for insertion of saidampoule into the housing with the needle directed axially outwardlyrelative to said opening until the pointed end of the needle in itspreinjection position is within the housing, detent means for coactingwith said abutments on said ampoule for yieldably restraining saidampoule against reverse movement toward said opening, and ampoule movingmeans operative first to move said ampoule past said detent means andtoward said housing opening for projecting the needle from the housingsubstantially for its exposed length in its preinjection position andthen for moving said ampoule plunger and needle toward said ampoulediaphragm with a continuing force sufficient to express the medicamentfrom said chamber through said needle and into a patient; wherebyoperation of said ampoule moving means of the applicator while the openend of the applicator is held against the skin of a patient first movessaid ampoule and needle to cause the needle to penetrate into thepatient for substantially the exposed length of the needle in saidpreinjection position and then moves said ampoule plunger toward said]ampoule diaphragm for further advancing the needle into the patientwhile expressing medicament from said ampoule chamber through saidneedle and into the patient, said housing including stop means forsubsequent positive restraining engagement with said abutments on saidampoule, said detent means and said stop means being discontinuouscircumferentially of said applicator housing to permit passage of saidampoule abutments thereby during insertion of the ampoule, andengagement of said abutments thereby after relative rotation of theinserted ampoule about a common axis of said housing and ampoule.

14. A hypodermic injection assembly according to claim 13 including acup-shaped needle guard removably secured to the diaphragm end 'of saidampoule, said guard having a bottom wall spaced from said diaphragm bya-distance exceeding the length of said end portion of the needle in itspreinjection position.

1. In a unitary hypodermic device of the contained-needle typecomprising a closed medicament-containing cylindrical glass ampoulehaving a pierceable wall at one end thereof, a hypodermic needle havinga pointed discharge end disposed in the ampoule for movement to pierceand project through said pierceable wall, and means for moving saidneedle through said pierceable wall while expressing medicament from theampoule therethrough; the improvement in which said ampoule has an outercircumferentially extending bead adjacent the pierceable wall endthereof, and said pierceable wall includes a relatively rigid annularouter portion frictionally retained by said bead and having an externalsurface configured to provide an annular, skin-engaging rim surroundinga concavely recessed surface portion that defines a central openingthereon and a cylindrical sidewall having an internal circumferentialgroove for receiving said bead and locking said outer portion to saidampoule, said cylindrical sidewall also including an end portion beyondsaid internal groove that snugly engages said cylinder about itscircumference inwardly of the bead thereon, and said bead havingopposite side portions that slope differently relative to the axis ofsaid cylinder to facilitate forcing said end portion of said outerportion over said bead when applying said outer portion to the cylinderand to render removal thereof by reverse movement more difficult; and aseparate relatively flexible pierceable inner diaphragm portion forclosing the end of said ampoule and held in position by said outerportion, said diaphragm portion having a central gland projectingoutwardly through said central opening in said outer portion andembracing the pointed discharge end of said needle, said annular rim andprojecting gland being axially related to be pressed, together, againstthe skin of the patient to tense the skin within the rim for increasingthe resistance of the skin to pressure from the gland and moreeffectively sealing the gland against the skin while urging the glandinwardly against the pointed end of the needle to facilitate piercing ofthe gland and the skin upon actuation of said needle-moving means.
 2. Ahypodermic ampoule according to claim 1 in which said cylindricalsidewall of said outer portion is sufficiently resistant to elasticdeformation to substantially prevent its removal without breaking saidampoule.
 3. A multichamber ampoule for mixing and dischargingmedicaments, comprising a first cylinder, a first diaphragm sealed toand closing one end of said first cylinder, a plunger slidably disposedin the other end of said first cylinder to provide a first chamberbetween said plunger and first diaphragm, a hollow needle disposed insaid first chamber for movement with said plunger toward said firstdiaphragm and having an open end adjacent said plunger and an oppositepointed discharge end adjacent said first diaphragm, and a powdermedicament in said first chamber; a second cylinder axially aligned withsaid first cylinder and having one end closed by insertion of said firstdiaphragm therein with a peripheral portion of the first diaphragm inaxial sliding engagement with the inner surface thereof, a seconddiaphragm closing the other end of said second cylinder, said first andsecond diaphragms and second cylinder, together, defining a secondchamber, and a fluid medicament in said second chamber; whereby saidfluid and solid medicaments may be mixed preparatory to dischargethereof by first moving said plunger and needle sufficiently toward saidfirst diaphragm to project the pointed end of the needle through saidfirst diaphragm to establish communication between the two chambers andby then moving said first cylinder, first diaphragm, plunger, and needleas a unit toward said second diaphragm to progressively reduce thevolume of said second chamber substantially to zero and thereby expresssaid liquid medicament through the needle into the first chamber whilebringing said first and second diaphragms substantially into engagementand disposing the pointed end of said needle in position to project theneedle through said second diaphragm upon further movement of saidplunger toward said first and second diaphragms the improvement in whichsaid second diaphragm comprises a pierceable wall having a relativelyrigid, annular, outer portion having an external surface configured toprovide an annular, skin-engaging rim surround a concavely recessedsurface portion that defines a central opening therein and a relativelyflexible, pierceable, inner diaphragm portion having a central glandprojecting outwardly through said central opening and embracing thepointed discharge end of said needle.
 4. A multichamber hypodermicampoule according to claim 3, wherein the outer diameter of said firstcylinder is less than the inner diameter of said second cylinder.
 5. Amultichamber hypodermic ampoule according to claim 3, wherein the volumeof said first chamber is substantially equal to the volume of saidsecond chamber.
 6. A multichamber hypodermic ampoule according to claim3, wherein the volume of said first chamber sufficiently exceeds thevolume of said second chamber so that the volume of the two medicamentsin said first chamber after mixing the medicaments therein issubstantially less than the remaining volume of said first chamber,whereby, prior to expelling the mixed contents of the first chamber,said plunger may be further advanced toward said first and seconddiaphragms to extend a portion of the length of said needle through andbeyond said second diaphragm in an exposed condition for projection intoa patient to the depth of muscle tissue to be injected, and said plungermay then be moved further toward said first and second diaphragms toprogressively expel the mixed contents of said first chamber throughsaid needle and into said muscle tissue while further advancing saidneedle into said muscle tissue.
 7. A multichamber hypodermic ampouleaccording to claim 3, in which at least one additional diaphragm isdisposed in said second chamber between said first and second diaphragmsso as to divide said second chamber into a plurality of smallerchambers, and a corresponding plurality of different liquid medicamentsrespectively substantially fill said smaller chambers, whereby each ofsaid liquid medicaments, one after another, may be caused to flowthrough said needle into said first chamber by progressive movement ofsaid first diaphragm, first cylinder, plunger, and needle, as a unit, tobring all of said diaphragms substantially into engagement with oneanother.
 8. A hypodermic ampoule comprising a cylinder; a plungerclosing one end of the cylinder with a sliding seal; a pierceablediaphragm closing the other end of the cylinder to provide a medicamentchamber therein; a hypodermic needle disposed in said chamber andextending axially thereof for movement with said plunger toward saiddiaphragm, said needle having an opening from the chamber into theneedle at one end thereof adjacent said plunger and an opposite,pointed, discharge end; and a clip secured to said other end of saidcylinder and having a bottom portion pressing said diaphragm into sealedengagement with that end of the cylinder; said diaphragm having anoutwardly extending central gland portion embracing the pointed end ofthe needle, and said bottom portion of said clip having an externalsurface configured to provide an annular, skin-engaging rim surroundinga concavely recessed surface portion defining a central opening thereinthrough which said diaphragm gland projects so that said clip rim andprojecting gland may be pressed, together, against the skin of a patientto tension the skin within the clip rim, whereby the skin firmly engagesthe gland to urge it inwardly and facilitate penetration of the glandand skin by the needle upon inward movement of said plunger to injecTmedicament through the needle and into the patient, a liquid medicamentpartially filling said chamber so as to leave an initial space betweensaid plunger and the medicament when the ampoule is vertically disposedwith the plunger end thereof uppermost, whereby the plunger may be movedinwardly to project the needle through and beyond said diaphragm glandprior to expressing liquid medicament through the needle, and whereinsaid plunger has a portion extending axially beyond the plunger end ofsaid cylinder for a distance substantially corresponding to the lengthof said space axially of the cylinder.
 9. A hypodermic ampoule accordingto claim 8, including a cup-shaped needle guard removably secured tosaid clip and having a bottom portion spaced from said gland an axialdistance substantially corresponding to the axial length of said initialspace between said plunger and medicament.
 10. A hypodermic ampouleaccording to claim 8, wherein said plunger and diaphragm are rubber andsaid cylinder is rigid and substantially transparent.
 11. A hypodermicampoule according to claim 8 in which said cylinder has an outer,circumferentially extending bead adjacent the diaphragm end thereof, andsaid clip is cup-shaped with a cylindrical sidewall embracing said beadand the adjacent end portion of the cylinder for securing the clip andsaid diaphragm to the cylinder.
 12. A hypodermic ampoule according toclaim 8 in which said cylinder is formed of glass and has an outer,circumferentially extending bead adjacent the diaphragm end thereof,said clip being cup-shaped with a generally cylindrical sidewallembracing said bead and the adjacent end portion of the cylinder, andsaid cylindrical sidewall of the clip having an internal,circumferential groove receiving said bead of said cylinder and lockingthe clip against removal.
 13. In a hypodermic injection assembly: a. acontained-needle type of hypodermic ampoule comprising a cylinder, apuncturable diaphragm closing and sealing one end of said cylinder, aslidable plunger in the opposite end of said cylinder and spaced fromsaid diaphragm to provide a chamber therebetween, a liquid medicament insaid chamber, and a hypodermic needle disposed in said chamber formovement by said plunger to a preinjection position in which a dischargeend portion of the needle has pierced and extends beyond said diaphragmin an exposed condition and thereafter to transmit medicament from saidchamber into a patient receiving an injection while moving furtherthrough said diaphragm, the volume of medicament in said chamber beingsubstantially less than the initial volume of said chamber to permitmovement of the plunger to project the needle to said preinjectionposition before expressing medicament from the chamber through theneedle, said diaphragm comprising a pierceable wall having a relativelyrigid, annular, outer portion having an external surface configured toprovide an annular, skin-engaging rim surrounding a concavely recessedsurface portion that defines a central opening therein and a relativelyflexible, pierceable, inner diaphragm portion having a central glandprojecting outwardly through said central opening and embracing thedischarge end of said needle; and said ampoule including radiallyprojecting abutments spaced about its periphery; b. an applicator foractuating said ampoule to perform an injection after the needle has beenprojected to its preinjection position, said applicator comprising ahousing having an open end for insertion of said ampoule into thehousing with the needle directed axially outwardly relative to saidopening until the pointed end of the needle in its preinjection positionis within the housing, detent means for coacting with said abutments onsaid ampoule for yieldably restraining said ampoule against reversemovement toward said opening, and ampoule moving means operative firstto move said ampoule past said detent means and toward said housingopening for projecting the needle frOm the housing substantially for itsexposed length in its preinjection position and then for moving saidampoule plunger and needle toward said ampoule diaphragm with acontinuing force sufficient to express the medicament from said chamberthrough said needle and into a patient; whereby operation of saidampoule moving means of the applicator while the open end of theapplicator is held against the skin of a patient first moves saidampoule and needle to cause the needle to penetrate into the patient forsubstantially the exposed length of the needle in said preinjectionposition and then moves said ampoule plunger toward said ampoulediaphragm for further advancing the needle into the patient whileexpressing medicament from said ampoule chamber through said needle andinto the patient, said housing including stop means for subsequentpositive restraining engagement with said abutments on said ampoule,said detent means and said stop means being discontinuouscircumferentially of said applicator housing to permit passage of saidampoule abutments thereby during insertion of the ampoule, andengagement of said abutments thereby after relative rotation of theinserted ampoule about a common axis of said housing and ampoule.
 14. Ahypodermic injection assembly according to claim 13 including acup-shaped needle guard removably secured to the diaphragm end of saidampoule, said guard having a bottom wall spaced from said diaphragm by adistance exceeding the length of said end portion of the needle in itspreinjection position.